on September 9, 2002
Hypertension. 2002
Published online before print September 9, 2002, doi: 10.1161/01.HYP.0000034738.79310.06
Published online before print September 9, 2002, doi: 10.1161/01.HYP.0000034738.79310.06
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Submitted on May 31, 2002
From the Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada. * To whom correspondence should be addressed. E-mail: schiffe{at}ircm.qc.ca.
Abstract—Angiotensin II plays an important role in vascular remodeling. We investigated the role of aldosterone, which is stimulated by angiotensin II, as a mediator of angiotensin II-induced vascular structural and functional alterations. Sprague-Dawley rats (n=8 to 12/group) received angiotensin II (120 ng/kg per minute, subcutaneously) for 14 days ± spironolactone or hydralazine (25 mg/kg per day). An additional group received aldosterone (750 ng/h, subcutaneously) ± spironolactone. Systolic blood pressure was increased by angiotensin II (P<0.001) and reduced by spironolactone and hydralazine (P<0.001). Aldosterone-induced increase of blood pressure was reduced by spironolactone (P<0.05). In mesenteric small arteries studied on a pressurized myograph, media/lumen ratio was increased (P<0.001) and acetylcholine-mediated relaxation was impaired in angiotensin II-infused rats (P<0.001); both were partially improved by spironolactone (P<0.05) but not by hydralazine. Aldosterone-induced increase of media/lumen ratio (P<0.001) and impaired response to acetylcholine (P<0.001) were normalized by spironolactone. Response to sodium nitroprusside was similar in all groups. Aortic NADPH oxidase activity was increased (P<0.01) by angiotensin II and reduced by spironolactone and hydralazine. Aldosterone also increased (P<0.05) activation of NADPH oxidase, an effect abolished by spironolactone. Plasma thiobarbituric acid-reactive substances (a marker of oxidative stress), higher in angiotensin II and aldosterone rats (P<0.001), were normalized by spironolactone. In conclusion, spironolactone, which inhibited aldosterone actions, partially corrected structural and functional angiotensin II-induced abnormalities. These effects were associated with reduced vascular NADPH oxidase activity and decreased plasma markers of oxidative stress. Our findings suggest that aldosterone may mediate some of angiotensin II-induced vascular effects in hypertension, in part via increased oxidative stress.
Revised on June 24, 2002
Spironolactone Improves Angiotensin-Induced Vascular Changes and Oxidative Stress
Agostino Virdis;
Key words: aldosterone • angiotensin II • endothelium • hypertension, arterial • oxidative stress • remodeling • rats
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E. L. Schiffrin The Many Targets of Aldosterone Hypertension, May 1, 2004; 43(5): 938 - 940. [Full Text] [PDF]
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A. Nishiyama, L. Yao, Y. Nagai, K. Miyata, M. Yoshizumi, S. Kagami, S. Kondo, H. Kiyomoto, T. Shokoji, S. Kimura, et al. Possible Contributions of Reactive Oxygen Species and Mitogen-Activated Protein Kinase to Renal Injury in Aldosterone/Salt-Induced Hypertensive Rats Hypertension, April 1, 2004; 43(4): 841 - 848. [Abstract] [Full Text] [PDF]
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K. T. Weber From Inflammation to Fibrosis: A Stiff Stretch of Highway Hypertension, April 1, 2004; 43(4): 716 - 719. [Full Text] [PDF]
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F. K Shieh, E. Kotlyar, and F. Sam Aldosterone and cardiovascular remodelling: focus on myocardial failure Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1): 3 - 13. [Abstract] [PDF]
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S. Arima, K. Kohagura, H.-L. Xu, A. Sugawara, A. Uruno, F. Satoh, K. Takeuchi, and S. Ito Endothelium-Derived Nitric Oxide Modulates Vascular Action of Aldosterone in Renal Arteriole Hypertension, February 1, 2004; 43(2): 352 - 357. [Abstract] [Full Text] [PDF]
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F. Aguilar, M. Lo, B. Claustrat, J. M. Saez, J. Sassard, and J. Y. Li Hypersensitivity of the Adrenal Cortex to Trophic and Secretory Effects of Angiotensin II in Lyon Genetically-Hypertensive Rats Hypertension, January 1, 2004; 43(1): 87 - 93. [Abstract] [Full Text] [PDF]
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R. A. Ahokas, K. J. Warrington, I. C. Gerling, Y. Sun, L. A. Wodi, P. A. Herring, L. Lu, S. K. Bhattacharya, A. E. Postlethwaite, and K. T. Weber Aldosteronism and Peripheral Blood Mononuclear Cell Activation: A Neuroendocrine-Immune Interface Circ. Res., November 14, 2003; 93 (10): e124 - e135. [Abstract] [Full Text] [PDF]
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E. Ritz and V. Haxsen Angiotensin II and Oxidative Stress: An Unholy Alliance J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2985 - 2987. [Full Text] [PDF]
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B. Pitt Aldosterone Blockade in Patients With Systolic Left Ventricular Dysfunction Circulation, October 14, 2003; 108(15): 1790 - 1794. [Full Text] [PDF]
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Z. Ungvari, A. Csiszar, A. Huang, P. M. Kaminski, M. S. Wolin, and A. Koller High Pressure Induces Superoxide Production in Isolated Arteries Via Protein Kinase C-Dependent Activation of NAD(P)H Oxidase Circulation, September 9, 2003; 108(10): 1253 - 1258. [Abstract] [Full Text] [PDF]
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A. Schafer, D. Fraccarollo, S. K Hildemann, P. Tas, G. Ertl, and J. Bauersachs Addition of the selective aldosterone receptor antagonist eplerenone to ACE inhibition in heart failure: effect on endothelial dysfunction Cardiovasc Res, June 1, 2003; 58(3): 655 - 662. [Abstract] [Full Text] [PDF]
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